Magnetic resonance activatable thermosensitive liposomes for controlled doxorubicin delivery

Mater Sci Eng C Mater Biol Appl. 2020 Oct:115:111116. doi: 10.1016/j.msec.2020.111116. Epub 2020 May 25.

Abstract

To limit the massive cytotoxicity of chemotherapeutic agents, it is desirable to establish an appropriate subtle blend of formulation design based on a dual-responsive strategy. In this study, a combined therapeutic platform based on magnetic thermosensitive liposomes (LipTS-GD) was developed. The incorporation of chelated-gadolinium imparted magnetic properties to thermosensitive liposomes (LipTS). The application of an ultra high field magnetic resonance imaging (UHF-MRI) induced hyperthermia, thus provided an improved chemotherapeutic effect of Doxorubicin (DOX). The paramagnetic platform demonstrated thermal sensitivity over a narrow temperature range starting at 37.8 °C, hence the release of DOX from LipTS-GD can be well triggered by inducing hyperthermia using UHF-MRI application. The prepared LipTS-GD were below 200 nm in diameter and an adequate release of DOX reaching 68% was obtained after 1 h UHF-MRI exposure. Profoundly, triple-negative breast cancer (TNBC) cells that were treated with LipTS-GD and subjected thereafter to UHF-MRI exposure for 60 min showed 36% viability. Hemocompatibility studies of LipTS-GD showed a physiological coagulation time and minimal hemolytic potential. Conclusively, LipTS-GD guided local delivery of DOX to solid tumors will potentially raise the therapeutic index, thus reducing the required dose and frequency of DOX administered systemically without influencing the adjacent tissues.

Keywords: Doxorubicin; Drug delivery; Thermosensitive liposomes; Triggered release; Ultra high field magnetic resonance imaging.

MeSH terms

  • Antibiotics, Antineoplastic / chemistry
  • Antibiotics, Antineoplastic / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Combined Modality Therapy
  • Doxorubicin / chemistry
  • Doxorubicin / pharmacology*
  • Drug Compounding
  • Female
  • Humans
  • Hyperthermia, Induced / methods*
  • Liposomes
  • Magnetic Resonance Imaging

Substances

  • Antibiotics, Antineoplastic
  • Liposomes
  • Doxorubicin